Portal Hypertension

Contents

Preface: Portal Hypertension xiii

Jorge L. Herrera

Pathophysiology of Portal Hypertension 281

Yasuko Iwakiri

Portal hypertension is a major complication of liver disease that resultsfrom a variety of pathologic conditions that increase the resistance tothe portal blood flow into the liver. As portal hypertension develops, theformation of collateral vessels and arterial vasodilation progresses, whichresults in increased blood flow to the portal circulation. Hyperdynamiccirculatory syndrome develops, leading to esophageal varices or ascites.This article summarizes the factors that increase (1) intrahepatic vascularresistance and (2) the blood flow in the splanchnic and systemic circula-tions in liver cirrhosis. In addition, the future directions of basic/clinicalresearch in portal hypertension are discussed.

Invasive and Noninvasive Methods to Diagnose Portal Hypertension andEsophageal Varices 293

Roberto de Franchis and Alessandra Dell’Era

Assessing the presence of clinically significant portal hypertension andesophageal varices is clinically important in cirrhosis. The reference stan-dard techniques to assess the presence of portal hypertension and varicesare the measurement of the hepatic vein pressure gradient and esophago-gastroduodenoscopy, respectively. Some newer methods have showna good performance, but none have been proven precise enough toreplace hepatic vein pressure gradient measurement or esophagogastro-duodenoscopy for the diagnosis of portal hypertension or the presenceand grade of esophageal varices.

Pharmacologic Management of Portal Hypertension 303

Annalisa Berzigotti and Jaime Bosch

Progress in the knowledge of the pathophysiology of portal hypertensionhas disclosed new targets for therapy, resulting in a larger spectrum ofdrugs with a potential role for clinical practice. This review focuses onpharmacologic treatments already available for reducing portal pressureand summarizes drugs currently under investigation in this field.

Role of Transjugular Intrahepatic Portosystemic Shunt in the Management ofPortal Hypertension 319

Richard Parker

A transjugular intrahepatic portosystemic shunt (TIPS) is an expandablemetal stent inserted via the jugular vein that creates a shunt from the portalvein to the systemic circulation via an artificial communication through the

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liver. It is used to treat complications of portal hypertension. In addition torescue treatment in variceal bleeding, TIPS can play an important role inprevention of rebleeding. TIPS can improve symptoms if medical treat-ment of ascites or hepatic hydrothrorax has failed, but may not improvesurvival. Selected cases of Budd-Chiari syndrome improve with TIPS.This article discusses the indications, evidence, and complications ofTIPS.

Primary Prophylaxis of Variceal Bleeding 335

Douglas A. Simonetto, Vijay H. Shah, and Patrick S. Kamath

Primary prevention of variceal bleeding is an important and long-debatedtopic in themanagement of patients with cirrhosis and esophageal varices.Prophylaxis is recommended for high-risk patients with small esophagealvarices (advanced liver disease and/or presence of red wale marks) andthose with medium/large varices. Nonselective b-blockers and endo-scopic band ligation have been shown to be equally effective in primaryprevention of variceal bleeding and are the only currently recommendedtherapies. Controversy still exists, however, regarding which one of thesestrategies is preferred. This article reviews the established recommenda-tions and recent advances in the prevention of first esophageal varicealbleeding.

Management of Acute Variceal Bleeding 347

Jorge L. Herrera

Endoscopic Band Ligation (EBL) of esophageal varices accompaniesthe article

Acute variceal bleeding (AVB) is the most common cause of upper gastro-intestinal hemorrhage in patients with cirrhosis. Advances in the manage-ment of AVB have resulted in decreased mortality. To minimize mortality,a multidisciplinary approach addressing airway safety, prompt judiciousvolume resuscitation, vasoactive and antimicrobial pharmacotherapy,and early endoscopy to obliterate varices is necessary. Placement ofa transjugular intrahepatic portosystemic shunt (TIPS) has been used asrescue therapy for patients failing initial attempts at hemostasis. Patientswho have a high likelihood of failing initial attempts at hemostasis maybenefit from a more aggressive approach using TIPS earlier in theirmanagement.

Secondary Prophylaxis for Esophageal Variceal Bleeding 359

Agustín Albillos and Marta Tejedor

Combination therapy with beta-blockers and endoscopic band ligation(EBL) is the standard prophylaxis of esophageal variceal rebleeding incirrhosis. Beta-blockers are the backbone of combination therapy, sincetheir benefits extend to other complications of portal hypertension. EBLcarries the risk of post-banding ulcer bleeding, which explains why overallrebleeding is reduced when beta-blockers are added to EBL, and notwhen EBL is added to beta-blockers. TIPS is the rescue treatment, but itcould be considered as first choice in patients that first bleed whileon beta-blockers, those with contraindications to beta-blockers or withrefractory ascites, and those with fundal varices.

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Gastric and Ectopic Varices 371

Zachary Henry, Dushant Uppal, Wael Saad, and Stephen Caldwell

Although often considered together, gastric and ectopic varices representcomplications of a heterogeneous group of underlying diseases. Com-monly, these are known to arise in patients with cirrhosis secondary to por-tal hypertension; however, they also arise in patients with noncirrhoticportal hypertension, most often secondary to venous thrombosis of theportal venous system. One of the key initial assessments is to define theunderlying condition leading to the formation of these portal-collateralpathways to guide management. In the authors’ experience, thesepatients can be grouped into distinct although sometimes overlappingconditions, which can provide a helpful conceptual basis of management.

Portal Hypertensive Gastropathy and Colopathy 389

Nathalie H. Urrunaga and Don C. Rockey

Portal hypertensive gastropathy (PHG) and colopathy (PHC) are consid-ered complications of portal hypertension. Both entities are clinically rele-vant because they may cause insidious blood loss or even acute massivegastrointestinal hemorrhage. Endoscopic evaluation is necessary for thediagnosis of PHG and PHC. The existence of different endoscopic criteriafor PHG and PHC makes consensus difficult and results in a broad rangeof reported prevalence. Therapy targeted at reduction of portal pressureand mucosal blood flow has been used to treat acute bleeding; nonselec-tive b-blockers are the most frequently used agents. Further studies areneeded to clarify the natural history, pathogenesis, and treatment ofPHG and PHC.

Hepatopulmonary Syndrome 407

David G. Koch and Michael B. Fallon

The hepatopulmonary syndrome (HPS) is a pulmonary complication of cir-rhosis and/or portal hypertension whereby patients develop hypoxemia asa result of alterations in pulmonary microvascular tone and architecture.HPS occurs in up to 30% of patients with cirrhosis. Although the degreeof hypoxemia does not reliably correlate with the severity of liver disease,patients with HPS have a higher mortality than do patients with cirrhosiswithout the disorder. There has been progress into defining the mecha-nisms that lead to hypoxemia in HPS, but to date there are no therapeuticoptions for HPS aside from liver transplantation.

Portopulmonary Hypertension 421

Rodrigo Cartin-Ceba and Michael J. Krowka

Portopulmonary hypertension (POPH) is the presence of pulmonary arte-rial hypertension in patients with portal hypertension. Among liver trans-plant (LT) candidates, reported incidence rates of POPH range from4.5% to 8.5%. In patients with LT, intraoperative death and immediatepost-LT mortality are feared clinical events when transplantation is at-tempted in the setting of untreated, moderate to severe POPH; therefore,POPH precludes LT unless the mean pulmonary artery pressure can bereduced to a safe level and right ventricular function optimized. Specific

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pulmonary artery vasodilator medications seem effective in reducingpulmonary artery pressures and improving right ventricular function andsurvival.

Hepatic Hydrothorax 439

John Paul Norvell and James R. Spivey

Hepatic hydrothorax (HH) is an uncommon complication in patients withend-stage liver disease. Only 5% to 10% of patients with end-stage liverdisease develop HH, which may result in dyspnea, hypoxia, and infection,and portends a poor prognosis. The most likely explanation for develop-ment is passage of fluid from the peritoneal space to the pleural spacedue to small diaphragmatic defects. Initial management consists of di-ureticswith dietary sodium restriction and thoracentesis, and a transjugularintrahepatic portosystemic shunt may ultimately be required. Afflictedpatients can develop morbid and fatal complications, pose managementdilemmas, and should warrant evaluation for liver transplantation.

Non-cirrhotic Portal Hypertension 451

Shiv K. Sarin and Rajeev Khanna

Non-cirrhotic portal hypertension (NCPH) encompasses a wide range ofdisorders, primarily vascular in origin, presenting with portal hypertension(PHT), but with preserved liver synthetic functions and near normal hepaticvenous pressure gradient (HVPG). Non-cirrhotic portal fibrosis/IdiopathicPHT (NCPF/IPH) and extrahepatic portal venous obstruction (EHPVO)are two prototype disorders in the category. Etiopathogenesis in both ofthem centers on infections and prothrombotic states. Presentation andmanagement strategies focus on repeated well tolerated episodes of var-iceal bleed and moderate to massive splenomegaly and other features ofPHT. While the long-term prognosis is generally good in NCPF, portal bil-iopathy and parenchymal extinction after prolonged PHT makes outcomesomewhat less favorable in EHPVO. While hepatic schistosomiasis, con-genital hepatic fibrosis and nodular regenerative hyperplasia have theirdistinctive features, they often present with NCPH.

Surgery in Patients with Portal Hypertension: A Preoperative Checklist andStrategies for Attenuating Risk 477

Gene Y. Im, Nir Lubezky, Marcelo E. Facciuto, and Thomas D. Schiano

Patients with liver disease and portal hypertension are at increased risk ofcomplications from surgery. Recent advances have allowed better optimi-zation of patients with cirrhosis before surgery and a reduction in postop-erative complications. Despite this progress, the estimation of surgicalrisk in a patient with cirrhosis is challenging. TheModel for End-Stage LiverDisease (MELD) score has shown promise in predicting postoperativemortality compared with the Child-Turcotte-Pugh score. This article ad-dresses current concepts in the perioperative evaluation of patients withliver disease and portal tension, including a preoperative liver assessment(POLA) checklist that may be useful towards mitigating perioperativecomplications.

Index 507